Cholesterol lipoprotein levels

Treatment Various drugs are available that have different mechanisms of action and effects on LDL (cholesterol) and VLDL (triglycerides) (A). Their use is indicated in the therapy of primary hyperlipoproteinemias. In secondary hyperlipoproteinemias, the immediate goal should be to lower lipoprotein levels by dietary restriction, treatment of the primary disease, or both. 

Liver toxicity is a rare side effect of CBZ therapy (Trimble, 1990), although a recent study reported that 9% of children on CBZ had mildly elevated aspartate aminotransferase (Camfield and Camfield, 1985). Higher mean serum total cholesterol (TC) levels, mean low-density lipoprotein level, and mean TC/high-density lipoprotein ratio have been reported in children with epilepsy treated with CBZ, compared with controls (Sozuer et ah, 1997). Conversely, an increase in serum high-density lipoproteins was reported in a smaller sample of patients treated with CBZ, and was therefore interpreted as a possible protective factor against atherosclerosis (Yalcin et ah, 1997). 

The major biochemical changes observed are a striking depletion of ATP, impaired protein synthesis, defective incorporation of amino acids, and the appearance of RNA and proteins containing the ethyl rather than the methyl group. The plasma levels of triglycerides, cholesterol, lipoprotein, and phospholipid are all decreased. 

Monounsaturated fats Triacylglycerols containing primarily fatty acids with one double bond are referred to as monounsaturated fat. Unsaturated fatty acids are generally derived from vegetables and fish. When substituted for saturated fatty acids in the diet, monounsaturated fats lower both total plasma cholesterol and LDL cholesterol, but increase HDLs. This ability of monounsaturated fats to favorably modify lipoprotein levels may explain, in part, the observation that Mediterranean cultures, with diets rich in olive oil (high in monounsaturated oleic acid), show a low incidence of coronary heart disease. 

Hyperlipidemia is a condition characterized by the presence of elevated lipoprotein levels in the blood. The term hyperlipidemia encompasses a number of different conditions, but it most often refers to high levels of cholesterol in the form of low-density lipoprotein (LDL). LDL cholesterol is often called bad cholesterol. High-density lipoprotein (HDL) is the good form of cholesterol. High LDL and/or low HDL levels are widely believed to be linked to increased heart disease risk. Because of the prevalence of hyperlipidemia in developed nations, antihyperlipidemic drugs are in high demand. 

Cholesterol can be obtained either from the diet or it can be synthesized de novo, mainly in the liver. Cholesterol is transported round the body in lipoprotein particles (see Topic K6). The rate of synthesis of cholesterol is dependent on the cellular level of cholesterol. High levels of cholesterol and its metabolites control cholesterol biosynthesis by ... 

The purpose of altering plasma lipoprotein levels is to reduce the risk of coronary events. The results of outcome trials are available for lovastatin (Downs et al, 1998), simvastatin (Scandinavian Simvastatin Survival Study Group 1994), and pravastatin (Shepherd et al, 1995 Sacks et al, 1996 The Long-Term Intervention With Pravastatin in Ischaemic Disease (LIPID) Study Group, 1998). Three of these trials, 4S, Cholesterol and Recurrent Events (CARE), and LIPID, studied patients with CHD, whereas the West of Scotland Coronary Revention Study Group and the Air Force Coronary Atherosclesosis Prevention Study (AFCAPS) evaluated the benefits of therapy in patients without known CHD. The main results of these trials are summarized in Tables la and lb. 

Estrogen replacement therapy has been found to lower serum levels low-density lipoprotein (LDL) cholesterol, lipoprotein (a), and apoliprotein B, and to increase serum levels of high-density lipoprotein (HDL) cholesterol and apolipoprotein A-l (PEPI Trial, 1995 Tikka-nen, 1996 Ylikorkala etal., 1995). 

Figure 13.2 Effect of inserting a human CETP gene on cholesterol lipoproteins in E3L mice fed a Western-type diet containing 0.25% cholesterol. The E3L.hCETP mouse has shown to respond to statins, fibrates, and the new CETP inhibitor torce-trapib in a similar way as humans do, as manifested by decreased apoB-containing lipoproteins and increased HDL levels.

Benzoxazole and triazole derivatives 67 and 73b showed the highest antiatherosclerotic activity among all the investigated silacyclic S-sub-stituted heterocycles in mice maintained on high-cholesterol diet. They protected against an increase in serum low-density lipoprotein level and... 

Dietary MUFA have been found to have several positive effects that include, in addition to lowering human LDL-cholesterol plasma levels, positive effects on lipoprotein oxidation, coagulation, and fibrinolysis (29). Low-fat, monounsaturate-rich diets reduce the susceptibility of low-density lipoproteins to peroxidation ex vivo (30). In hypercholesterolemic subjects, diets containing MUFA resulted in favorable alterations in the fatty acid composition and oxidative profile of LDL in hypercholesterolemic subjects that were characterized as an increase in lipid peroxide lag time and a decrease in lipid peroxide formation (30). In animal studies. 

On the other hand, Mutanen et al. (128) found that canola oil and sunflower oil enhanced in vitro platelet aggregation. Similarly, McDonald et al. (113) found that both canola oil and sunflower oil increased prostacyclin production (an antiaggregating eicosanoid) and decreased thromboxane production (a proaggregating eicosanoid). Although the effect of canola oil on platelet activity and clot formation is not as well established as its favorable effect on plasma cholesterol and lipoprotein levels, there is evidence that it may impede clot formation. 

Absorption, digestion, and metabolism studies have been conducted on caprenin (21, 22). Several clinical studies suggested that, despite its lower energy content, caprenin slightly increased lipoprotein levels. In one study, with 30 adult males fed caprenin at 34 g/day for eight weeks, total serum cholesterol, LDL, and HDL were increased by 8%, 20%, and 13%, respectively (23). 

The recent finding that lower, rather than higher, cholesterol levels are associated with poor clinical outcome in patients with chronic heart failure has lead to hypothesise an important role of endotoxins, and the ensuing inflammation induced by it, in the atherosclerotic lesion progression. The ability of lipoproteins to bind endotoxins and to serve as natural buffer substances may explain the relationship between lower lipoprotein levels, higher cytokine concentrations and impaired prognosis [18]. 

Baggio, G., Pagnan, A., Muraca, M., Martini, S., Opportune, A., Bonanome, A., Ambrosio, G., Ferrari, S., Guarini, R, Piccolo, D., Manzato, E., Corrocher, R., and Crepaldi, G. (1988). Olive-oil-enriched diet Effect on serum lipoprotein levels and biliary cholesterol saturation. Am. J. Clin. Nutr. 47, 960-964. 

A combination of bile acid sequestrants with nicotinic acid or probucol or an HMG-CoA reductase inhibitor can be used to produce synergistic effects in lowering plasma lipoprotein levels, particularly LDL. The efficacy of drug treatment was shown in a recent study in which lovas-tatin and colestipol were used to reduce cholesterol levels in men with CHD. The rate of progression of coronary lesions was decreased and that of regression increased. These changes also were associated with reduced cardiovascular abnormalities. 

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